The alveolar epithelium functions as a barrier, separating the water and solute of the interstitial and vascular spaces of the lung from the air space of the alveoli. When this barrier function fails in pulmonary edema either the integrity of the epithelium has been disrupted, or the pathologic conditions have superseded the capacity of epithelium to restrict water and solute from the alveoli. Rational development of new therapy for pulmonary edema depends on elucidation of the status of the alveolar epithelium, whether it has decompensated or been disrupted. Utilizing methods that have successfully characterized the alveolar epithelium in normal animals, this project will define the changes on the alveolar epithelium barrier on a biophysical level in experimental pulmonary edema. In anesthetized dogs in vivo transfer constants across the alveolar epithelium will be derived for several lipid-insoluble, non-electrolyte solutes of known molecular radius. Transfer is measured by the change in concentration of radiolabeled test substances in a saline solution infused into the left lung, which is also statically inflated during the experiment. Using the equivalent pore model for solute and water transfer across biologic membranes, the radius of equivalent pores will be determined during a control period. Pulmonary edema will be induced by partial aortic occlusion and transfusion, and the transfer of the labeled solutes determined during pulmonary edema. Analysis of the differences of rates of transfer of these molecular probes during pulmonary edema, from the control period, will indicate whether the alveolar epithelium has been disrupted allowing unrestricted diffusion or changed allowing increased, but still restricted, diffusion.